Age is a major risk factor for severe coronavirus disease-2019 (COVID-19). Here, we interrogate the transcriptional features and cellular landscape of the aging human lung. By intersecting these age-associated changes with experimental data on SARS-CoV-2, we identify several factors that may contribute to the heightened severity of COVID-19 in older populations. The aging lung is transcriptionally characterized by increased cell adhesion and stress responses, with reduced mitochondria and cellular replication. Deconvolution analysis reveals that the proportions of alveolar type 2 cells, proliferating basal cells, goblet cells, and proliferating natural killer/T cells decrease with age, whereas alveolar fibroblasts, pericytes, airway smooth muscle cells, endothelial cells and IGSF21+ dendritic cells increase with age. Several age-associated genes directly interact with the SARS-CoV-2 proteome. Age-associated genes are also dysregulated by SARS-CoV-2 infection in vitro and in patients with severe COVID-19. These analyses illuminate avenues for further studies on the relationship between age and COVID-19.1,2-Bis-silyl alkenes have exciting synthetic potential for programmable sequential synthesis via manipulation of the two vicinal silyl groups. Transition metal-catalyzed bis-silylation of alkynes with disilanes is the most straightforward strategy to access such useful building blocks. However, this process has some limitations (1) symmetric disilanes are frequently employed in most of the reactions to assemble two identical silyl groups, which makes chemoselective differentiation for stepwise downstream transformations difficult; (2) the main catalysts are low-valent platinum group transition metal complexes, which are expensive; and (3) internal alkynes remain challenging substrates with low inherent reactivity. Thus, the development of abundant metal-catalyzed bis-silylation of internal alkynes with unsymmetrical disilanes is of significance. Herein, we solve most of the aforementioned limitations in bis-silylation of unsaturated bonds by developing a strongly coordinating disilane reagent and a Ni(0) catalytic system. Importantly, we sufficiently realize the stepwise recognition of the two silyl groups, making this synthetic protocol of wide potential utility.Environmental triggers have important functions in multiple sclerosis (MS) susceptibility, phenotype, and trajectory. Exposure to early life trauma (ELT) has been associated with higher relapse rates in MS patients; however, the underlying mechanisms are not well-defined. Here we show ELT induces mechanistic and phenotypical alterations during experimental autoimmune encephalitis (EAE). ELT sustains downregulation of immune cell adrenergic receptors, which can be attributed to chronic norepinephrine circulation. ELT-subjected mice exhibit interferon-β resistance and neurodegeneration driven by lymphotoxin and CXCR2 involvement. These phenotypic changes are observed in control EAE mice treated with β1 adrenergic receptor antagonist. Conversely, β1 adrenergic receptor agonist treatment to ELT mice abrogates phenotype changes via restoration of immune cell β1 adrenergic receptor function. Our results indicate that ELT alters EAE phenotype via downregulation of β1 adrenergic signaling in immune cells. These results have implications for the effect of environmental factors in provoking disease heterogeneity and might enable prediction of long-term outcomes in MS.Oxford Nanopore (ONT) is a leading long-read technology which has been revolutionizing transcriptome analysis through its capacity to sequence the majority of transcripts from end-to-end. This has greatly increased our ability to study the diversity of transcription mechanisms such as transcription initiation, termination, and alternative splicing. However, ONT still suffers from high error rates which have thus far limited its scope to reference-based analyses. When a reference is not available or is not a viable option due to reference-bias, error correction is a crucial step towards the reconstruction of the sequenced transcripts and downstream sequence analysis of transcripts. In this paper, we present a novel computational method to error correct ONT cDNA sequencing data, called isONcorrect. IsONcorrect is able to jointly use all isoforms from a gene during error correction, thereby allowing it to correct reads at low sequencing depths. https://www.selleckchem.com/products/apd334.html We are able to obtain a median accuracy of 98.9-99.6%, demonstrating the feasibility of applying cost-effective cDNA full transcript length sequencing for reference-free transcriptome analysis.Inflammation and cell death are closely linked arms of the host immune response to infection, which when carefully balanced ensure host survival. One example of this balance is the tightly regulated transition from TNFR1-associated pro-inflammatory complex I to pro-death complex II. By contrast, here we show that a TRIF-dependent complex containing FADD, RIPK1 and caspase-8 (that we have termed the TRIFosome) mediates cell death in response to Yersinia pseudotuberculosis and LPS. Furthermore, we show that constitutive binding between ZBP1 and RIPK1 is essential for the initiation of TRIFosome interactions, caspase-8-mediated cell death and inflammasome activation, thus positioning ZBP1 as an effector of cell death in the context of bacterial blockade of pro-inflammatory signaling. Additionally, our findings offer an alternative to the TNFR1-dependent model of complex II assembly, by demonstrating pro-death complex formation reliant on TRIF signaling.The spin of a single electron in a semiconductor quantum dot provides a well-controlled and long-lived qubit implementation. The electron charge in turn allows control of the position of individual electrons in a quantum dot array, and enables charge sensors to probe the charge configuration. Here we show that the Coulomb repulsion allows an initial charge transition to induce subsequent charge transitions, inducing a cascade of electron hops, like toppling dominoes. A cascade can transmit information along a quantum dot array over a distance that extends by far the effect of the direct Coulomb repulsion. We demonstrate that a cascade of electrons can be combined with Pauli spin blockade to read out distant spins and show results with potential for high fidelity using a remote charge sensor in a quadruple quantum dot device. We implement and analyse several operating modes for cascades and analyse their scaling behaviour. We also discuss the application of cascade-based spin readout to densely-packed two-dimensional quantum dot arrays with charge sensors placed at the periphery.